The objective of the proposed study is to determine whether different viral etiologies are associated with specific epigenetic changes in a particular type of cancer. Using the hepatocellular carcinoma (HCC) as a model system, we will characterize gene-specific hypermethylation changes present in HBV and HCV infections caused HCCs. We hypothesize that unique gene-specific hypermethylation patterns are associated with HBV and HCV caused HCCs. Further gene-specific hypermethylation present in HCCs from different geographic locations (China vs. US) do not differ after adjusting for viral infections. This study will contribute to our understanding of how HBV and HCV infections lead to HCC development. Successful completion of these studies will provide insight into the molecular pathogenesis of HCC and may lead to the identification of novel biomarkers for early detection of HCCs and the development of novel chemotherapeutic strategies against HCCs.